Obesity causes frailty in obese older adults by exacerbating the age-related decline in physical function. However, appropriate management of obesity in older adults is controversial. Weight loss without exercise could worsen frailty by accelerating the usual age-related decline in muscle and bone mass that leads to sarcopenia and osteopenia, respectively. Because of the important problem of frailty in obese older adults, it would be important to determine the most efficacious approach in reducing, or even reversing frailty in this population. The primary objective of this proposal is to evaluate which distinct type of physical exercise (resistance, aerobic, or combined) is most efficacious in preventing the weight-loss-induced reduction in muscle and bone mass and reversing frailty in obese older adults. A total of 160 obese older adults will be randomized to 1) 10% weight loss + resistance training, 2) 10% weight loss + aerobic training, 3) 10% weight loss + aerobic/resistance training, and 4) non-weight loss control group for 6 months. We hypothesize that 1) weight loss + resistance training will cause a greater improvement in physical function than weight loss + aerobic training and weight loss + aerobic/resistance training, 2) weight loss + resistance training will cause a greater preservation of muscle mass than weight loss + aerobic/resistance training, whereas weight loss + aerobic training will cause a decrease in muscle mass, 3) weight loss + resistance training will stimulate bone formation more than resorption compared to weight loss + aerobic/resistance training and, thus, preserve BMD, whereas weight loss + aerobic training will decrease bone turnover and attenuate the loss of BMD, and 4) weight loss + resistance training a) will cause a greater decrease in TNF-1 and IL-6 and a greater increase in MGF in skeletal muscles than aerobic and aerobic/resistance training and that b) these anabolic effects will correlate with preservation of muscle protein synthesis (MPS) and muscle mass during weight-loss therapy. Our overarching hypothesis across aims is that obesity and aging have additive adverse effects on body composition (sarcopenic obesity) and physical function (frailty), mediated by their additive adverse effects on inflammation and MPS, which will, thus, be significantly improved by weight loss + resistance training. Therefore, to test this central hypothesis in an integrated manner, we will use partial correlation and multiple regression analyses, to determine which of the body composition factors and/or the mechanistic skeletal muscle factors are the most important mediators for the observed changes in physical function. Obesity in older adults is a major public health problem. The number of obese older adults in our society will continue to increase, challenging existing health care delivery systems. The results of this proposed RCT will have important implications for preventing the loss of functional independence of obese older adults in our society and, therefore, will change current clinical practice for this rapidly growing segment of the population. PUBLIC HEALTH RELEVANCE: Obesity in older adults is a major public health problem that provides a challenge to health care professionals and our existing health care delivery systems. Obesity worsens the decline in physical function that occurs with age, and increases the risk for loss of independence in the community. This study will determine the most efficacious approach towards preventing the loss of functional independence of obese older adults in our society and will change current clinical practice for this rapidly increasing segment of the population.